Intrathecal Administration of the α1 Adrenergic Antagonist Phentolamine Upregulates Spinal GLT-1 and Improves Mirror Image Pain in SNI Model Rats

Kosuke Nakatsuka, Yoshikazu Matsuoka, Masako Kurita, Ruilin Wang, Chika Tsuboi, Nobutaka Sue, Ryuji Kaku, Hiroshi Morimatsu

Research output: Contribution to journalArticlepeer-review

Abstract

Mirror image pain (MIP) is a type of extraterritorial pain that results in contralateral pain or allodynia. Glutamate transporter-1 (GLT-1) is expressed in astrocytes and plays a role in maintaining low glutamate levels in the synaptic cleft. Previous studies have shown that GLT-1 dysfunction induces neuropathic pain. Our previous study revealed bilateral GLT-1 downregulation in the spinal cord of a spared nerve injury (SNI) rat. We hypothesized that spinal GLT-1 is involved in the mechanism of MIP. We also previously demonstrated noradrenergic GLT-1 regulation. Therefore, this study aimed to investigate the effect of an α1 adrenergic antagonist on the development of MIP. Rats were subjected to SNI. Changes in pain behavior and GLT-1 protein levels in the SNI rat spinal cords were then examined by intrathecal administration of the α1 adrenergic antagonist phentolamine, followed by von Frey test and western blotting. SNI resulted in the development of MIP and bilateral downregulation of GLT-1 protein in the rat spinal cord. Intrathecal phentolamine increased contralateral GLT-1 protein levels and partially ameliorated the 50% paw withdrawal threshold in the contralateral hind paw. Spinal GLT-1 upregulation by intrathecal phentolamine ameliorates MIP. GLT-1 plays a role in the development of MIPs.

Original languageEnglish
Pages (from-to)255-263
Number of pages9
JournalActa medica Okayama
Volume76
Issue number3
DOIs
Publication statusPublished - Jun 1 2022

Keywords

  • alpha adrenergic receptor
  • glutamate transporter-1
  • mirror image pain
  • neuropathic pain
  • spared nerve injury

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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